The pursuit of new drug entities derived from plants and plant products for various therapeutic applications has its origins in antiquity and continues to the present. One such source is mastic, also known as gum mastic or mastic gum, which is a tree resin obtained as an exudate from Pistacia lentiscus L, a member of the family Anacardiaceae. Mastic was used in the ancient Mediterranean world for gastrointestinal disorders such as gastralgia, dyspepsia and peptic ulcer. Oral administration of mastic to human patients with duodenal ulcer and to experimental rats with induced gastric and duodenal ulcers has been disclosed to have therapeutic effects (Al-Habbal et al (1984) Clin Exp Pharmacop Physio 11(5):541-4; Said at al (1986) J Ethnopharmacol 15(3):271-8). While it has been disclosed that mastic has in vitro bactericidal effects against Helicobacter pylori, the etiologic agent causing peptide ulcer disease (Marone et at (2001) J Chemother 13:611-614), other reports disclose that mastic does not exert anti-bacterial activity upon administration to H. pylori positive human patients (Bebb et al (2003) J Antimicrob Chemother 52:522-23) or to experimentally infected mice (Loughlin et at (2003) J Antimicrob Chemother 51:367-371).
Greek Patent No. GR 1,003,541 discloses antimicrobial and antifungal action of the chios mastic oil extracted from the leaves, branches and fruit of Pistacia lentiscus var Chia.
Greek Patent No. GR 1,003,868 discloses use of a product derived from Pistacia lentiscus var. Chia as an antioxidant, as a wound healing inductor and as a cytostatic agent.
U.S. Patent Application Publication No 2005/0238740 is directed to Use of mastic and its components for the control of microbial infections.
Paraschos et al (2007), authored by some of the inventors of the aforementioned patent application, disclose preparation of a total mastic extract without polymer (TMEWP), prepared by polar solvent extraction of crude mastic and removal of the insoluble polymer poly-1-myrcene therefrom, and acidic and neutral fractions separated from TMEWP (Paraschos et al (2007) Antimicrob Agents Chemother 51(2):551-559). According to the disclosure, administration of TMEWP to H. pylori infected mice over a period of 3 months resulted in a 30-fold reduction of bacterial colonization, largely attributable to a particular compound purified from the acid fraction. The authors indicate that TMEWP was prepared since the high percentage of poly-β-myrcene in crude mastic preparations, as used in previous studies, was speculated to hinder potential in vivo activity during oral administration. The authors further disclose that removal of the poly-β-myrcene can produce an enhanced therapeutic moiety with anti-H. pylori activity.
EP Patent Application No. 1520585 is directed to Cancer treatment using natural plant products or essential oils or components from some pistacia species.
International Patent Application Publication No. WO 2005/112967 is directed to anticancer activity of chios mastic gum.
Van der Berg et al (1998) disclose isolation and purification of the polymer fraction of mastic using extraction and size exclusion chromatography (Van der Berg et al (1998) Tetrahedron Lett 3:2645-2648).
Barra et al (2007) disclose extraction and gas chromatographic analysis of essential oil from P. lentiscus L. (Barra et al (2007) J Agric Food Chem 55(17):7093-7098). According to the disclosure, a total of 45 compounds were identified, including β-myrcene as one of the major compounds.
International Patent Application Publication No. WO 2010/100650 to some of the inventors of the present invention, is directed to therapeutic uses of mastic gum fractions.
International Patent Application Publication No. WO 2010/100651 to some of the inventors of the present invention, is directed to compositions of polymeric myrcene.
International Patent Application Publication No. WO 2005/094837 is directed to Use of masticadienoic acid as inhibitor of DNA polymerase-beta, used for treating cancers, tumors and neurodegenerative diseases.
Marner et al (1991) disclose identification of various triterpenoids from gum mastic of P. lentiscus (Marner et al (1991) Phytochemistry, 30, 3709-3712).
Giner-Larza et al (2002) disclose anti-inflammatory triterpenes from pistacia terebinthus galls (Planta Med (2002), 68, 311-315).
Nevertheless, there remains an unmet need for safe, versatile and effective agents for treatment of various conditions, such as those associate with impaired neurological functions and related neurodegenerative conditions, including, for example, Alzheimer's disease, stroke, and the like, as well and other conditions, such as tissue regeneration, wound and tissue repair.